CATIONIC IMPREGNATION BY HEAVY METAL SALTS OF BREAST TISSUE ENHANCES SOFT-TISSUE MAMMOGRAPHIC IMAGES

The winter meeting of the YVessex Branch of the Association of Clinical Pathologists was held on 10 December 1992 at the Postgraduate Centre, Southmead Hospital. After the business meeting (President: J D Davies; Secretary: E F Mackenzie; Treasurer: N B N Ibrahim), and a scheduled address by a member of the Executive Committee of the Royal College of Pathologists, the following oral papers were presented by trainee pathologists from the South West Region.

porphyrins derived from the haem moiety of haemoglobin was used to quantify blood loss in faeces.
Patients receiving thrombolytic therapy streptokinase or thromboplasminogen activator following myocardial infarction were studied. Haemoglobin levels in random faecal samples were compared with controls, who did not receive thrombolysis, admitted to the CCU during the same time period.
Mean peak measured faecal haemoglobin in the treatment group (n = 36) was 5.09 mg/g stool (SD = 7.50, SE = 1.25) and in the control group (n = 19) was 1.45 mg/g (SD = 1.30, SE = 0.30). The difference was statistically significant (p <0.05). 25/36 (69%) in the treatment group and 2/19 (10.5%) in the control group had levels greater than 2 mg/g, the quoted upper limit of normal, in at least one sample. It is concluded that thrombolytic therapy is associated with increased GI blood loss although in none of the patients studied was the magnitude sufficient to cause haemodynamic compromise.
There are circumstances under which quantitative determination of faecal blood loss should be considered advantageous because of the limited sensitivity and specificity of the traditional, qualitative, guaiac impregnated slide tests.
Porphyrin fluorescence analysis is a practical alternative to radioisotopic labelling of red blood cells to achieve this. The potential for metastasis of melanoma can be assessed using clinical and histological prognostic variables and several prognostic models have been developed.The precision of such microstaging depends on the number and power of variables although a few of these such as thickness are sufficiently powerful to be considered as single variables in clinical use.
One hundred histological reports of excision specimens of stage 1 invasive melanomas from files were analysed to see how often basic histological features were recorded. None of the one hundred reports contained all the relevant histological data. In 15% of the reports there was no comment on the degree of excision. In many of the reports microstage attributes that have been shown to be prognostically important much as mitotic count or ulceration were omitted. A standard method of reporting invasive melanomas is advocated which includes these attributes and will allow some degree of survival probability to be made.

Department of Clinical Chemistry Southmead Hospital
This study compared the sensitivity and specificity of various markers used to make the diagnosis of myocardial infarction. 50 patients admitted to a coronary care unit with a history of chest pain had frequent blood samples and ECG's taken during the first 24 hours. The ECGs were read blind by a cardiologist and the venous samples, after being stored at -70C, were analysed for Creatine Kinase, CK-MB, Myoglobin and Troponin-T. A full clinical history was obtained and a record was kept of all tests initiated by the admitting physicians and the diagnosis they reached on the basis of those tests. Data are presented outlining the ECG/biochemical criteria used to make the diagnosis, the misdiagnosis rate and the mortality rate in the different groups. The sensitivity and specificity of the individual markers were reviewed. A control group of 25 patients without chest pain had 6 hourly blood samples and a minimum of 1 ECG during the first 24 hours. The development of techniques such as Southern blotting, in situ hybridisation, northern blotting and the polymerise chain reaction (PCR) have led to the identification and understanding of consistent molecular "events" within certain disease processes. These techniques and events can be used as diagnostic aids. The histological differentiation between benign and malignant lymph node biopsies and extra-nodal lymphoid infiltrates is notoriously difficult. One of the best ways of identifying malignancy is to show monoclonality. During differentiation of lymphocytes one "event" is rearrangement of the T cell receptor (TCR) gene and the Immunoglobulin (Ig) gene. Each rearrangement is cell specific This presentation shows development of PCR to aid diagnosis in lymphoid malignancy. DNA has been extracted from as little as 3x5 micron thick sections of formalin fixed tissue. The suitability of the DNA for amplification has been tested by amplifying the HGPRT gene. To show monoclonality of a given lymphocyte population the CDR III region of the Ig heavy chain gene has been amplified. This region undergoes both nucleotide insertion and point mutation during rearrangement. Thus each lymphocyte has a unique CDR III size and sequence. The presence of a single sized band on electrophoresis after PCR is evidence of monoclonality. The success with fixed tissue means that archival material is now available for analysis and research. Mucocoele-like tumours of the breast have only recently been recognised as a morphological entity. They consist of expanded duct-like spaces filled with mucin, which often extravasates into the adjacent connective tissue. Initially they Were regarded in the United States as a benign and incidental finding. Later reports have demonstrated association wit atypical ductal hyperplasia and mucoid carcinoma.

MUCOCOELE-LIKE TUMOURS
We report two cases. One was found as an impalpa e ^ammographic lesion in the national Breast Screening Programme, and the other was detected in a retrospective survey 0f cases indexed as "benign fibrocystic disease . nortly afterwards the second case, diagnosed 10 years ago, was found to have an invasive carcinoma of non-mucinous type. Neither impalpability nor association with a nonmucinous carcinoma have been recorded before. We pr?Pose consideration of a contrary interpretation of mucocoele-like Umours: it would seem prudent to regard them as ductal carcinomas in situ of mucin-secreting type. It  Metal wear debris formation is a well known complication of joint replacement. There is concern that these metals, which are known in other situations to have both toxic and carcinogenic properties, might be responsible for local tumours and the increased risk of lymphoma and leukaemia that have been described in patients with hip replacements. In this study post mortem tissues from five patients with joint replacements and six control patients were studied with light and electronmicroscopy and mass spectometry. Our results show a greatly elevated level of metals, including Nickel, Chromium, Cobolt and Iron, in the lymph nodes, liver and spleen of patients with joint replacements.No accumulation was found in other organs including lung, kidney and brain. These metals were derived from the surface of the implant and were stored within macrophages. We conclude that there is a specific accumulation of metals at those sites shown to be at risk of carcinogenisis in the literature. Whilst there is no direct proof that metal in the form of debris is toxic or carcinogenic there must be concern about its accumulation in the reticulo-endothelial system, especially in younger arthoplasty patients. An antimicrobial peptide called Lactoferricin has recently been described by a research group from Japan. Tomita et al produced the peptide by acid-pepsin hydrolysis of bovine lactoferrin, and iron-binding protein also found in tears, gastric juice, genital and bronchial secretions. Tomita et al demonstrated that Lactoferricin has antimicrobial activity and subsequently they went on to sequence the peptide. The purpose of this study was to confirm Tomita's findings and expand on his work including clinical investigations. Lactoferricin was kindly supplied by Tomita of the Morinaga Milk Industry Japan. The purity of the supplied Lactoferricin was confirmed by HPLC and internal sequencing, this work was done in collaboration with Dr. Bloomberg at the Biochemistry Department of the University of Bristol. A wide range of organisms were tested and activity was demonstrated against both gram negative and gram positive organisms.
Yeasts were also sensitive to Lactoferricin.
The inoculum and ionic strength were found to be important variables; Lactoferricin's activity was markedly decreased when inoculae or ionic strengths were used. The results obtained so far confirm all the findings of Tomita et al. In addition we have produced data for more organisms demonstrating a wide spectrum of activity but also showing that not all organisms are susceptible and that there is a significant amount of strain variation within species. The clinical significance of these findings may be wide ranging. Of particular interest is the possibility that Lactoferricin is actually produced in the infants stomach following a milk feed resulting in a degree of antimicrobial activity in the small intestine. It is worth noting that human milk contains a higher concentration of lactoferrin/lOOg dry weight than cow's milk.

Could Lactoferricin be the reason why breast is best?
Lactoferrin is also found in many other bodily secretions, it may therefore be possible to find Lactoferricin there also.

SALTS OF BREAST TISSUE ENHANCES SOFT-TISSUE MAMMOGRAPHIC IMAGES
E K. Dankwa, J D Davies* Cambridge Military Hospital, Aldershot, and The Regional Breast Pathology Unit, Bristol BS10 5NB Preliminary radiography of slices from breast biopsies draws attention to relevant pathological changes underlying niammographic abnormalities. Nearly a third of the lesions are due to fibro-parenchymal changes (mass lesions or distortions of architecture). They cause many difficulties in appropriate grey-scaling if quantitative morphometric analysis is contemplated. In pilot studies we have found that post fixational impregnation of breast tissue by 2% w/v metallic salt solutions appears to improve radiological contrast of the fibroparenchymal tissue in slice mammograms of specimens.
We now report a detailed and replicated (n = 14 to 16) study using eleven metal containing inorganic salts undertaken before and after possible radiological enhancement using radiographs of reduction mammoplasty tissue (kindly supplied by the Department of Histopathology at Frenchay Hospital), the changes in radiographic density (assessed in a variety of modes by CUE2 densitometry software, Messrs. Olympus) of the fibro-parenchymal tissue showed the following approximate ranked order of radiodensity enhancement for fibro-parenchymal tissue by salts containing: Hg, Pb, Ur, Zn, Teaching of medical students is aided by all manner of computers and electronic gadgetry. One part of student teaching which has not changed in Pathology is the use of food terms in descriptive macroscopic pathology. These food terms were established many years ago. They now bear little relationship to the modern medical students diet to the extent that most medical students are unaware of the appearance of these foods, or indeed, in the case of sago, are unaware that it may be eaten at all! We presented 30 medical students with a questionnaire which was designed to record an individual student's knowledge of the relationship between a classical appearance of disease and a food substance. 92% of students had seen the diseased organ which fitted the description, but had not seen the related food item. Indeed many students did not know what the related food item was! This study highlights the need for change in this small but important aspect of the teaching of descriptive pathology. Modernisation of food terms to comply with the world of modern diet should be carried out in the pathological text books forthwith. The study of the colitis-carcinoma sequence has been hampered by the lack of a suitable model. The cottontop tamarin (a New world primate) is unique in developing a spontaneous colitis which bears a close resemblance to human ulcerative colitis as assessed clinically, endoscopically, histologically and in its response to treatment. It also develops liver disease closely resembling sclerosing chlangitis. 23 cases of colonic carcinoma complicating established ulcerative colitis in the tamarin are reported. All were flat and mucinous. The majority were right-sided. All showed early local spread with involvement of the pancreaticoduodenal lymph node. In 3 cases the tumours were microscopic but had produced lymph node metastases. The only differences between these animal tumours and those complicating human ulcerative colitis are: 1) lack of hepatic metastases, and 2) relative rarity ( For a few days it was a glorious distraction from the aims and the targets, the muddles and the meetings. For a few days we were able to argue and discuss a matter of such importance that Management was moved to act fast to prevent serious harm coming to the local people. The first inkling of a problem came at nine o clock on a Monday morning, The Redruth diabetic clinic has long been the breeding ground for martyrs; set in a medical no man s 'and, the watershed between West Cornwall and Truro, it is Possible for the doctor there exiled to feel strangely protected from attack. The impossible task of modifying recalcitrant behaviour away from all support allows one to feel distanced from other problems, Telephone calls pleading medical disasters elsewhere in the district can be met with a spiritual ca'ni normally requiring limbic doses of Glenmorangie.
1 have to admit that a call so soon after the start of the clinic did stir a faint unease. Even in the seconds before hearing the v?ice it is possible to consider enough trouble to cause real concern; too early for GPs to have got a new problem but too ate for a residual mess from the weekend. Curiously profound relief at hearing the voice of the Penzance nursing officer, army trained, straight to the point, frontal assault.
Had I seen it?" "No" There had been complaints from The Public, what was I 8?ing to do about it?" t Nothing, I haven't seen it.," Had I chosen it?" ' but I wish I had.
^ When was 1 coming back to Penzance?" Hmmm not until late evening," I'm beginning to enJ?y this.
A morning diabetic clinic followd by an afternoon gastroenterology clinic leaves numbness, the state in which best to admire the pointed breasts, the handless, footless and faceless naked bodies, the 8'x4" canvas vibrant and challenging. Over the last four years we have been lucky to be able to display the works of contemporary Newlyn School artists on the hospital corridor walls' I have been happy to let the gallery make the choice each year' Clearly it was felt that we were now able to appreciate nude female forms in joyful outdoor callisthenics.
It is easy to imagine the impact of 'Les Demoiselles d'Avignon' in 1906. Eighty six years later you may find it harder to understand the embarrassment and anger which was caused by our innocent painting.
The exchanges over the next two days became steadily less coherent and more acrimonious.
"The public don't want to see this sort of thing.
"But it was chosen by gallery staff who are members of the public".
"That's different; they're interested in art." "Ah yes." "You don't expect to see naked women in a hospital." "Really?" "Think how it could upset a patient who's had a mastectomy." "The mastectomy nurse thinks it's very good." "Shut up!" Only three complainants were ever identified, all members of staff, but a manager was persuaded to have the picture removed, The subsequent gentle outrage from the considerable numbers who resented the censorship was some compensation. A replacement picture by the same artist was not a threat to decency; 1 wonder though whether the hospital gardener wouldn't complain about those aggressive looking plants. Here he comes now Go on, make my day. 89